Inflammatory bowel disease

Refers to 2 chronic diseases that cause inflammation of the intestine: Ulcerative Colitis + Crohn’s disease

Chronic inflammatory bowel disease (IBD) that can affect any area of the gastrointestinal tract, from the mouth to the anus Cause is unknown Periods of exacerbations (inflammation) + remissions Inflammation is across the whole wall of GI tract Fissuring ulcers form (contents can leak out) Damage caused by inflammation leads to submucosal fibrosis (body trying to repair) Dense infiltration of lymphocytes + macrophages

Inflammation affects mucosal (inner) layer of the colon + rectum Cause ulcers Loss of goblet cells (secretes mucus) Infiltration of inflammatory cells into mucosa Unknown cause

Diarrhoea - impaired absorption Pain Narrowing of the gut lumen leading to strictures + bowel obstruction Abscess formation Fistulization to skin + internal organs

Inflammation leads to scar tissue formation Narrowing of lumen + obstruction Risk of rupture Pain, cramping, bloating

Inflammation leads to ulcers Ulcers develop into tunnels Between areas of GIT or between organs or to skin (anal fistulae)

Weight loss Macronutrient deficiencies Micronutrient deficiencies (minerals, calcium, iron) Fatigue Protein-energy malnutrition in 20-80% of patients

Severe diarrhoea - changes in electrolytes Blood loss Loss of peristaltic function leading to rigid colonic tube Toxic megacolon, perforation + sepsis

Joints, eyes, skin, mouth + liver Forms of IBD (inflammatory bowel disease) Risk of colon cancer (especially in u.colitis)

Drugs to reduce inflammatory response 5-aminosalicylate Steroids (corticocosteroids) Immunosuppressants

Inhibits leukotriene + prostanoid synthesis Scavenge free radicals (prevent them damaging cells) + decrease neutrophil chemotaxis (movement of neutrophil to site of infection) - effects on PPARy receptor Sulfasalazine metabolised to mesalazine Absorbed in small intestine but doesn’t reach colon

Anti-inflammatory, immunosuppressive actions e. g. oral prednisolone e. g. budesonide - poorly absorbed so fewer systemic side effects Used to induce remission Enemas used for more distal/rectal inflammation e.g. predfoam

Aazathioprine + methotrexate inhibit purine synthesis + DNA synthesis Reduce inflammatory cell proliferation Azathioprine is converted to mercaptopurine (purine derivative) - inhibits purine synthesis Cyclosporine inhibits InterLeukin-2 induced gene expression • used in refractory disease

One way merceptopurine is metabolised is by Thiopurine methyltransferase Some patients have low TPMT Some patients have no TPMT (risk of drug-induced bone marrow toxicity) Some patients have high TPMT (risk of mercaptopurine resistance)

Tumour necrosis factor alpha or TNFα is a cytokine. Cytokines are substances released by the body during inflammation.

‘manufactured’ monoclonal antibody binds to TNFalpha + prevent from causing inflammation Neutralises inflammatory cytokine TNF-alpha • associated w/ TB risk (antibodies are peptides which will be broken down if given orally) Infliximab = infusion Adalimumab = injection

Basic (elemental feeds) nutrition - can induce remission Reduce steroid use in severe Crohn’s Use parenteral support Small bowel removal - shortened bowel • reduce absorption • require nutritional support

Ulcerative colitis is caused by the upset of colonic bacteria

Monotherapy Add-on treatment Biological therapy/in severe active Crohn’s

Using a conventional glucocorticosteroid • prednisolone • methylprednisolone • intravenous hydrocortisone Alternative = budesonide/5-ASA

First line = azathioprine or mercaptopurine to a conventional glucocorticosteroid or budesonide to induce remission of Crohn’s disease Second line = Methotrexate

Infliximab/adalimumab

Taken once a day in the morning after food Avoid contact w/ people that have shingles, chickenpox or measles Carry steroid treatment card if taking oral corticosteroids for > 3 weeks Could have mood/behavioural changes Cannot stop abruptly Lifestyle recommendations to minimise side effects include: • adequate dietary intake • good nutrition • maintain normal body weight • smoking cessation • moderate alcohol consumption • physical exercise

Long-term effects of turnover of cells Increased risk of bleeding, bruising, sore throat, fever, malaise (should be reported) Enteric-coated tablets should be swallowed whole Laxatives must be taken at least 2 hours before or after taking EC tablets Sulfasalazine may colour tears yellow + urine orange + contact lenses to change colour